Real-world heart failure patients representative of those enrolled in the Phase 3 study of the Comprehensive Approach to Reduction of Adverse Cardiac Outcomes through Improved Contractility in Heart Failure (GALACTIC-HF) were considered a high-risk population with Significant Unmet need study presented at the Heart Failure Society of America (HFSA) Virtual Annual Scientific Meeting 2020.
The GALACTIC-HF study was an event-driven cardiovascular outcomes clinical study that evaluated omecamtiv mecarbil in patients with heart failure with reduced ejection fraction.
Cytokinetic researchers used de-identified electronic health records from 2006 to 2016 to conduct an analysis of outcomes in heart failure patients in real words with similar characteristics to the study population.
Patient records reflected inpatient and outpatient patients at Vanderbilt University Medical Center and were separated into 2 cohorts.
The clinical cohort included 3955 patients who matched the HFrEF eMERGE network phenotype, with a left ventricular ejection fraction (LVEF) ≤ 40%.
A similar GALACTIC-HF cohort included 1541 patients who met the eligibility criteria for those under study. These criteria included hospitalizations, medications, laboratory values, and LVEF ≤ 35%.
Therefore, approximately 40% of real-world HFrEF patients from their database had met the eligibility criteria for the GALACTIC-HF study.
The median age at index data for the clinical cohort was 65 years and 61 for the GALACTIC-HF-like cohort. Furthermore, both cohorts were approximately 66% male and 80% white.
Blood pressure and heart rate were similar between groups, but the similar GALACTIC-HF cohort demonstrated a higher median N-terminal type B (NT-proBNP) level (821 pg / m2) than the clinical cohort ( 506 pg / mL).
The researchers also noted that comorbidities were slightly higher in the GALACTIC-HF-like group. These comorbidities included chronic kidney disease (31% vs 21% in the clinical group) and atrial fibrillation (32% vs 23%).
Higher use rates of cardiac resynchronization or implantable cardioverter defibrillator were also observed in the GALACTIC-HF-like cohort compared to the clinical group (26% vs 23%, respectively).
Finally, the hospitalization rate for heart failure (per 1000 patient-years) was 396 (95% CI, 350-442) in the GALACTIC-HF-like cohort and 242 (95% CI, 203-280) in the clinical cohort. during a median follow-up of 4.1 and 2.7 years, respectively.
Also presented at HFSA 2020 were the results of a post-hoc analysis of the Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF), a phase 2 clinical study that evaluated omecamtiv mercarbil in patients with HFrEF.
These results suggested that the treatment improved right ventricular function in these patients.
Originally, the double-blind study evaluated left atrial and left ventricular function in patients with stable symptomatic heart failure and an LVEF <40%.
All 48 patients were randomly assigned 1: 1: 1 to receive omecamtiv mecarbil 25 mg twice daily, 25 mg – 50 mg of the same treatment twice daily with pharmacokinetic (or group) guided dose selection. PK titration) or placebo for 20 weeks.
Post-hoc analysis found that patients in the PK titration group demonstrated improved measures of right ventricular function.
These measures included right ventricular systolic ejection time (RV-SET) (P.<.001), right ventricular end-systolic area (RV-ESA) (P. = .012) and speed integral time of the right ventricular outflow tract (RVOT-VTI) (P = .002).
In addition, the analysis showed improvements in right ventricular pulmonary arterial coupling measures.
“These analyzes of real-world patients comparable to those on GALACTIC-HF and who are at high risk for cardiovascular events, including hospitalization, support the design of our Phase 3 clinical trial to evaluate the potential for omecamtiv mecarbil in patients. with unmet clinical needs, ”Fady I. Malik, MD, Ph.D., Cytokinetics Executive Vice President of Research and Development, said in a statement.
“Additionally, although we have previously reported that omecamtiv mecarbil treatment improved left atrial and left ventricular function in COSMIC-HF patients, these additional data suggest that right ventricular function could also be improved, highlighting a potential for a more comprehensive on general heart function. “